Mesothelioma shows promising response to existing immunotherapy drug

An existing immunotherapy drug called pembrolizumab appears to be effective in the treatment of malignant pleural mesothelioma, a rare and aggressive lung cancer that is primarily caused by exposure to asbestos. Writing in The Lancet Oncology, researchers describe the first study to show a positive result from using the antibody drug against this rare cancer.

Malignant mesothelioma - commonly referred to as mesothelioma - is a rare cancer that arises in the mesothelium, the thin lining of tissue that covers the inside of the chest, the heart, the abdomen, and most internal organs.

Malignant pleural mesothelioma - in which tumors form in the pleura, the linings of the chest wall and lungs - is an aggressive cancer that accounts for 90 percent of malignant mesothelioma cases. Unfortunately, most patients do not survive for longer than a year.

The main risk factor for malignant pleural mesothelioma is inhalation of asbestos, and most cases in the United States have been linked to work-related exposure to high levels of the material.

Asbestos is a naturally occurring mineral that was once commonly used to make materials for a wide range of industries, including home and commercial construction. In the U.S., many buildings erected before 1980 contain asbestos, the fibers of which can become dislodged into the air through normal wear and tear.

When asbestos is inhaled, the tiny fibers travel to the ends of the small airways and enter the pleura that line the chest wall and lungs. The fibers damage the mesothelial cells and cause scarring (asbestosis), cancer (mesothelioma), or both.

Poor prognosis and no second-line treatments

One of the reasons that patients diagnosed with mesothelioma have such poor prospects is because the disease is often not spotted until it is well advanced.

Fast facts about mesothelioma

Around 3,000 new cases of mesothelioma are diagnosed in the U.S. each year.

Rates of mesothelioma have leveled off and even reduced slightly in the U.S. in recent decades.

The standard treatment is first-line therapy that includes chemotherapy. There are currently no approved second-line treatments.

Researchers have looked at several other approved drugs, but the new study is the first to show promising results, as Dr. Evan Alley, lead author and chief of hematology and medical oncology at the Penn Presbyterian Medical Center of the University of Pennsylvania Health System in Philadelphia, explains:

"There have been a lot of studies looking at different drugs, but researchers have not seen positive results. But we've found this new class of drugs, checkpoint inhibitors, seems to be more effective than what's been available in the past."

Checkpoint inhibitors are drugs designed to help the body fight cancer by defeating certain mechanisms that cancer cells use to avoid being attacked by the immune system.

Some cancer cells have large amounts of a protein called PD-L1, which can bind to the checkpoint protein PD-1 on cancer-fighting T cells of the immune system. When this happens, it stops the T cell from attacking the cancer cell that the PD-L1 belongs to.

Pembrolizumab - which in the U.S. has the brand name Keytruda - is a drug that targets PD-1 and improves the immune response against cancers that are positive for PD-L1. It is already used to treat non-small cell lung cancer, melanoma, and some head and neck cancers.

Pembrolizumab promising as second-line therapy

In their study, Dr. Alley and colleagues use data from an ongoing multicenter international clinical trial that is testing the effectiveness and safety of pembrolizumab on patients with advanced PD-L1-positive solid tumors that have not responded to first-line treatment or for which treatment is not appropriate.

The data they assess concern 25 patients with malignant pleural mesothelioma, all over the age of 18. Upon enrolment - which started 2 years ago - patients received a dose of pembrolizumab every 2 weeks.

The results show that 14 of the patients experienced tumor shrinkage. Average overall survival was 18 months, during which around 6 months was progression-free. Since the start of the study, 14 patients have died and four were still receiving treatment as the researchers wrote up the results.

Dr. Alley sees these results as very promising: "Most patients who receive a second-line therapy have a life expectancy of about 6 or 7 months, so to have four patients still ongoing at 2 years is very encouraging."

He adds that another encouraging result is the fact that none of the patients had to stop the immunotherapy because of side-effects. Some had to stop for a while, but they then resumed. "The drug appears to be well-tolerated," he notes.

The common adverse reactions that the patients reported were dry mouth, nausea, fatigue, and loss of appetite.

More studies are now needed to support the findings before pembrolizumab can be considered as a second-line therapy for malignant pleural mesothelioma. Some have already started, and Dr. Alley says that there are also plans to start testing pembrolizumab with other treatments later this year.

"This study provides evidence that some patients can have long-term disease control with this drug, which we haven't seen before. We need to better understand what we can do next to make immunotherapy more effective for more patients."